{"product_id":"crbnmidi-s41-e187-d249-i426","title":"Recombinant \u003cb\u003eCRBNmidi\u003c\/b\u003e (S41-E187_GSG_D249-I426), Cereblon, E3 Ligase","description":"\u003cp\u003e\u003cmeta charset=\"UTF-8\"\u003e \u003cmeta content=\"width=device-width, initial-scale=1.0\" name=\"viewport\"\u003e\u003c\/p\u003e\n\u003cstyle\u003e\n    \/* 1. VARIABLEN \u0026 RESET *\/\n    :root {\n        --primary-color: #0dbaad;\n        --text-dark: #373636;\n        --border-light: #e0e0e0;\n    }\n\n    * { margin: 0; padding: 0; box-sizing: border-box; }\n\n    .container {\n        max-width: 1200px;\n        margin: 0 auto;\n        background-color: white;\n        padding: 20px;\n        font-family: \"Source Sans Pro\", sans-serif;\n        color: var(--text-dark);\n        line-height: 1.6;\n    }\n\n    \/* 2. 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AKKORDEON \u0026 INNEN-ÜBERSCHRIFTEN *\/\n    .accordion-container {\n        border-top: 1px solid var(--border-light);\n        margin: 20px 0;\n    }\n    .accordion-item {\n        border-bottom: 1px solid var(--border-light);\n    }\n    .accordion-header {\n        width: 100%;\n        padding: 20px 0;\n        background: none;\n        border: none;\n        display: flex;\n        justify-content: space-between;\n        align-items: center;\n        font-family: inherit;\n        font-size: 25px;\n        color: var(--primary-color) !important; \/* Türkis für Haupt-Header *\/\n        text-transform: uppercase;\n        cursor: pointer;\n        text-align: left;\n    }\n\n    \/* Styling für h4 Überschriften im Scientific Context *\/\n    .content-inner h4 {\n        color: var(--primary-color) !important;\n        text-transform: uppercase;\n        margin: 20px 0 10px 0;\n        font-size: 20px;\n    }\n\n    .icon { position: relative; width: 20px; height: 20px; flex-shrink: 0; margin-left: 10px; }\n    .icon::before, .icon::after {\n        content: '';\n        position: absolute;\n        background-color: currentColor;\n        transition: transform 0.3s ease;\n    }\n    .icon::before { width: 100%; height: 2px; top: 50%; left: 0; transform: translateY(-50%); }\n    .icon::after { width: 2px; height: 100%; left: 50%; top: 0; transform: translateX(-50%); }\n    .accordion-item.active .icon::after { transform: translateX(-50%) rotate(90deg); opacity: 0; }\n\n    .accordion-content {\n        max-height: 0;\n        overflow: hidden;\n        transition: max-height 0.5s cubic-bezier(0, 1, 0, 1);\n    }\n    .accordion-item.active .accordion-content {\n        max-height: 4000px;\n        transition: max-height 1s ease-in-out;\n    }\n    .content-inner { padding: 15px 0 35px 0; font-size: 19px; }\n\n    .sequence-box {\n        word-break: break-all;\n        font-family: monospace;\n        background: #f4f4f4;\n        padding: 15px;\n        font-size: 15px;\n        border-left: 4px solid var(--primary-color);\n        margin-top: 10px;\n    }\n\n    \/* 5. MOBILE ANPASSUNGEN *\/\n    @media (max-width: 600px) {\n        .product-top-section {\n            flex-direction: column;\n            align-items: center;\n        }\n        .image-column {\n            order: -1;\n            margin-bottom: 20px;\n            width: 100%;\n        }\n        .side-image {\n            margin-top: 0;\n            margin-left: auto;\n            margin-right: auto;\n        }\n        .custom-list { font-size: 17px; }\n        .accordion-header { font-size: 20px; }\n    }\n\/* 6. INTRO TEXT SEKTION *\/\n    .intro-section {\n        margin: 20px 0;\n        font-size: 19px; \/* Desktop Größe *\/\n        line-height: 1.8;\n    }\n\n    \/* Mobile Anpassung für den Intro-Text *\/\n    @media (max-width: 600px) {\n        .intro-section {\n            font-size: 17px; \n            text-align: left;\n            padding: 0 5px;\n        }\n    }\n  \n\u003c\/style\u003e\n\u003cdiv class=\"container\"\u003e\n\u003cdiv class=\"product-top-section\"\u003e\n\u003cdiv class=\"info-column\"\u003e\n\u003cul class=\"custom-list\"\u003e\n\u003cli\u003eCrystallizable\u003c\/li\u003e\n\u003cli\u003eSmartSoak  \u003csup\u003e®\u003c\/sup\u003e   established\u003c\/li\u003e\n\u003cli\u003ePurity \u0026gt; 95%\u003c\/li\u003e\n\u003cli\u003eMonodisperse\u003c\/li\u003e\n\u003cli\u003eMelting temperature of 41°C\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"image-column\"\u003e\u003cimg class=\"side-image\" alt=\"Quality Plus Siegel\" src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/Stempel-QUALITY-PLUS-new.png?v=1771953936\"\u003e\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr\u003e\n\u003cdiv class=\"intro-section\"\u003e\n  \u003cp\u003eThe ubiquitin E3 ligase Cereblon (CRBN) is part of the ubiquitin–proteasome system and recruits substrates for protein degradation. It is a common target of Proteolysis-Targeting Chimeras (PROTACs), which have rapidly emerged as a leading modality in proximity-based therapeutics, leveraging the ubiquitin–proteasome system to eliminate proteins by enforcing proximity between an E3 ligase like CRBN and a protein of interest. \u003cbr\u003e\u003cbr\u003e\nOur recombinant CRBNmidi protein is of high, crystallography-grade quality and is well suited for researchers pursuing the development of novel PROTAC strategies.\n  \u003c\/p\u003e\n \u003c\/div\u003e \n\n  \n\u003cdiv class=\"accordion-container\"\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003econstruct design\u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003eCRBNmidi (Kroupova et al., 2024) is a truncated CRBN construct that enables sufficient expression of soluble and stable protein in \u003ci\u003eE. coli\u003c\/i\u003e without additional factors. The truncated CRBNmidi still retains functionality similar to full-length wild-type CRBN and is therefore ideal for crystallographic and biophysical studies of CRBN-based PROTACs.\u003c\/p\u003e\n\u003cp style=\"margin-top: 15px;\"\u003eCRBNmidi contains the Lon protease-like domain (Lon), spanning residues 41 - 187, followed by a Gly-Ser-Gly (GSG) linker that partially replaces the HB domain and connects the Thalidomide Binding Domain (TBD), which spans residues 249-426. The CRBNmidi construct also includes 12 stabilizing mutations (C78I, I92V, K116N, Q134E, R283W, C287N, V293S, G302D, L342R, C343E, T359I, L423I).\u003c\/p\u003e\n\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/CRBN_midi_ConstructDesign.png?v=1769178738\" alt=\"CRBN midi Construct Design\" style=\"max-width: 100%; height: auto; margin-top: 20px;\" class=\"responsive-img\"\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eProtein Properties \u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003e\u003cb\u003eProtein Construct:\u003c\/b\u003e S_A41-E187\/D249-I426\u003cbr\u003e\u003cb\u003eSource:\u003c\/b\u003e Human\u003cbr\u003e\u003cb\u003eExpression Host:\u003c\/b\u003e \u003ci\u003eEscherichia coli\u003c\/i\u003e\u003cbr\u003e\u003cb\u003eMolecular weight [kDa]:\u003c\/b\u003e 37.44\u003cbr\u003e\u003cb\u003epI:\u003c\/b\u003e 5.8\u003cbr\u003e\u003cb\u003eExtinction Coefficient [M\u003csup\u003e-1\u003c\/sup\u003ecm\u003csup\u003e-1\u003c\/sup\u003e]:\u003c\/b\u003e 46410\u003cbr\u003e\u003cb\u003eConcentration:\u003c\/b\u003e 3.6 mg\/mL\u003cbr\u003e\u003cb\u003eStorage Buffer:\u003c\/b\u003e 20 mM HEPES pH 7.5, 500 mM NaCl, 0.5 mM TCEP \u003cbr\u003e\u003cb\u003eTag:\u003c\/b\u003e none\u003c\/p\u003e\n\u003cp style=\"margin-top: 15px;\"\u003e\u003cb\u003eAmino acid sequence:\u003c\/b\u003e\u003c\/p\u003e\n\u003cdiv class=\"sequence-box\"\u003eSAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSIQVIPVLPQVMMILVPGQTLPLQLFHPQEVSMVRNLIQNDRTFAVLAYSNVQEREAEFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPEGSGDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYWVAANLPIDDSLRIQLLKIDSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSREGPMAAYVNPHGYVHEILTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALIPTI\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eQuality Plus\u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003e\u003cb\u003eQC Data:\u003c\/b\u003e \u003ca href=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/CRBNmidi_datasheet.pdf?v=1772445180\" target=\"_blank\"\u003eDatasheet\u003c\/a\u003e\u003cbr\u003e\u003cb\u003ePurity SDS:\u003c\/b\u003e \u0026gt;95 % \u003cbr\u003e\u003cb\u003eHydrodynamic Radius (nm):\u003c\/b\u003e 3.34\u003cbr\u003e\u003cb\u003ePolydispersity Index (PDI): \u003c\/b\u003e 0.24\u003cbr\u003e\u003cb\u003eT\u003csub\u003eon\u003c\/sub\u003e (°C):\u003c\/b\u003e 40.5\u003cbr\u003e\u003cb\u003eT\u003csub\u003em\u003c\/sub\u003e (°C):\u003c\/b\u003e 41.49\u003cbr\u003e\u003cb\u003eCalculated Mass [Da]:\u003c\/b\u003e 34325.368 \u003cbr\u003e\u003cb\u003eMeasured Mass [Da]:\u003c\/b\u003e 34323.39\u003c\/p\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eScientific context \u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003ch4\u003eStructure and function\u003c\/h4\u003e\n\u003cp\u003eCereblon (CRBN) functions as the substrate receptor of the Cullin 4–RING E3 ubiquitin ligase complex by coupling target recognition to ubiquitin transfer. Through its C-terminal thalidomide-binding domain, CRBN directly engages its substrates, bringing them and ubiquitin-loaded E2 into close proximity and positioning the target for polyubiquitination.\u003cbr\u003e\n  \u003cbr\u003e\nIts native targets include many important endogenous substrates, such as adenosine monophosphate-activated protein kinase subunit α1, amyloid precursor protein or glutamine synthetase.\u003c\/p\u003e\n  \u003cbr\u003e\n\u003ch4\u003eCRBN as important drug target\u003c\/h4\u003e\n\u003cp\u003eCRBN and its associated E3 ubiquitin ligase are central to targeted protein degradation strategies with significant therapeutic potential. Immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide act as molecular glues that enable CRBN to recruit new substrates (neosubstrates), leading to their ubiquitination and degradation, which has diverse anti-cancer and immunmodulatory effects. \u003cbr\u003e\u003cbr\u003e\nMoreover, CRBN-binding ligands have been adapted for the development of PROTACs that induce the degradation of specific clinically relevant targets, underscoring the importance of CRBN in modern drug discovery.\n\n\u003c\/p\u003e\n\u003cdiv style=\"font-size: 15px; margin-top: 25px; border-top: 1px dotted #ccc; padding-top: 15px;\"\u003e\n\u003cb\u003eReferences:\u003c\/b\u003e\n  \n  \u003cbr\u003eKroupava, Alena. (2024) Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders. Nature communications. DOI: \u003ca href=\"https:\/\/doi.org\/10.1038\/s41467-024-52871-9\" target=\"_blank\"\u003e10.1016\/j.bpj.2021.04.015\u003c\/a\u003e\u003cbr\u003e\n   \u003cbr\u003eTao, Jing. (2018). The interacting domains in cereblon differentially modulate the immunomodulatory drug-mediated ubiquitination and degradation of its binding partners. Biochemical and Biophysical Research Communications. DOI: \u003ca href=\"https:\/\/doi.org\/10.1016\/j.bbrc.2018.11.058\" target=\"_blank\"\u003e10.1016\/j.bpj.2021.04.015\u003c\/a\u003e\u003cbr\u003e\n\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cp\u003e \u003c\/p\u003e","brand":"CrystalsFirst Shop","offers":[{"title":"1 mg","offer_id":56746341368191,"sku":null,"price":1500.0,"currency_code":"EUR","in_stock":true},{"title":"5 mg","offer_id":56746341400959,"sku":null,"price":6750.0,"currency_code":"EUR","in_stock":true},{"title":"10 mg","offer_id":56746341433727,"sku":null,"price":12000.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/CRBN-purple.jpg?v=1778612855","url":"https:\/\/shop.crystalsfirst.com\/products\/crbnmidi-s41-e187-d249-i426","provider":"CrystalsFirst GmbH","version":"1.0","type":"link"}